Prenatal Exposure to Perfluoroalkyl Substances is Associated with Lower Hand, Foot and Mouth Disease Viruses Antibody Response in Early Childhood: Novel Findings from the Guangzhou Birth Cohort Study

Background: Hand Foot and Mouth Disease (HFMD) is a common, global childhood viral infection of which the incidence has substantially increased in the Asia-Pacific region paralleling the rise in exposure to perfluoroalkyl substances (PFASs). These two phenomena may be related. There is evidence that PFASs exposure is associated with immune system disruption in early life. We conducted the world's first study to assess whether prenatal exposure to PFAS was associated with a reduction in HFMD virus antibodies in early childhood. Methods: We enrolled 201 mother-infant pairs from the Guangzhou Birth Cohort Study in 2013.  PFAS isomer-specific analysis based on high performance liquid chromatography-mass spectrometry assessed the concentrations of PFAS isomers in cord blood. Neutralizing antibodies titers were measured against two HFMD viruses, enterovirus 71 (EV71) and coxsackievirus A 16 (CA16), in serum in cord blood and at three months of age. Findings: Higher prenatal PFAS exposure was associated with lower EV71 and CA16 antibody concentrations. A doubling in the composite sum of cord blood PFASs in three months old infants was associated with significant increase in the risk of HFMD antibody concentration below clinical protection level (>1:8 titers) for CA16 (odds ratio: 2·740 [95% confidence interval (CI): 1·33, 5·61] and for EV71 of 4·55 (95% CI: 1·45, 4·28). This association was apparent in boys at three months of age. Funding Statement: This project was supported by Grants from the National Natural Science Foundation of China (No.81472936, No. 81673127 and No. 81172630), Major Infectious Disease Prevention and Control ofthe National Science and Technique Major Project (2018ZX10715004), the Project for KeyMedicine Discipline Construction of Guangzhou Municipality (No. 2017–2019–07), theFundamental Research Funds for the Central Universities (No. 17ykzd14), the Natural ScienceFoundation of Guangdong Province (No. 2016A030313342) and the State Key Laboratory of Organic Geochemistry, GIGCAS (No. SKLOG–201608). The above funding has not taken control of the study design  Declaration of Interests: The authors declare that they have no conflicts of interest. Ethics Approval Statement: Informed consent was obtained from participants. This study protocol was approved by the Institutional Review Board (Sun Yat–sen University Research Ethics Committee), and all study procedures were in accordance with the principles of Helsinki Declaration.